Polyreactivity of antibody molecules

The ’lock and key’ hypothesis of antigen–antibody interaction has long dominated immunological thinking. However, studies demonstrating the existence of a large number of monoclonal antibodies that can bind to a variety of totally unrelated self and foreign antigens (i.e. polyreactive antibodies) has modified this view. We argue that the best explanation for polyreactivity is that the antigen-binding ‘pocket’ of many antibody molecules is more flexible than previously thought and can change conformation to accommodate different antigens. In terms of biological function, we discuss the evidence for and against a role for polyreactive antibodies in immunological defense. We speculate that, paradoxically, because B cells that make polyreactive antibodies are capable of binding to many different endogenous host antigens, they might be involved in the induction and/or maintenance of immunological tolerance.